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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
17 October to 01 November 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP study conducted in compliance with OECD Guideline No. 405 without deviation.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted 24 April 2002
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
UK GLP Compliance Programme (inspected on July 10, 2012/ signed on November 30, 2012)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Physical state: Pale yellow liquid
- Storage condition of test material: Approximately 4 °C in the dark under nitrogen

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Remarks:
Hsdlf:NZW
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Leicestershire, UK.
- Age at study initiation: 12-20 weeks
- Weight at study initiation: 2.55-2.99 kg
- Housing: Animals were individually housed in suspended cages.
- Diet: Food (2930C Teklad Global Certified Rabbit diet supplied by Harlan Laboratories UK Ltd., Oxon, UK), ad libitum.
- Water: Mains drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17-23 °C
- Humidity: 30-70 %
- Air changes: 15 changes/h
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: 17 October to 01 November 2012

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): Undiluted
Duration of treatment / exposure:
No washing was done
Observation period (in vivo):
1, 24, 48 and 72 h after instillation of test item
Number of animals or in vitro replicates:
3 males
Details on study design:
PRETREATMENT
- Immediately before the start of the test, both eyes of the provisionally selected test rabbits were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope. Only animals free of ocular damage were used.

PROCEDURE
- Initially, a single rabbit was treated. A volume of 0.1 ml of the test item was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test item, and then released. The left eye remained untreated and was used for control purposes. Immediately after administration of the test item, an assessment of the initial pain reaction was made according to the six point scale shown in Appendix 1.
- After consideration of the ocular responses produced in the first treated animal, two additional animals were treated.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No

SCORING SYSTEM: Draize scale as described in the OECD guideline No. 405.

TOOL USED TO ASSESS SCORE: Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.

OTHERS
- Individual bodyweights were recorded on Day 0 (the day of dosing) and at the end of the observation period.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.3
Max. score:
2
Reversibility:
fully reversible within: 48 h
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 h
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 h
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.7
Max. score:
3
Reversibility:
fully reversible within: 72 h
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
- No corneal effects were noted during the study.
- Iridial inflammation was noted in one treated eye one and 24 hours after treatment.
- Moderate conjunctival irritation was noted in all treated eyes one hour after treatment. Moderate conjunctival irritation was noted in one treated eye with minimal conjunctival irritation noted in two treated eyes at the 24 hour observation. Minimal conjunctival irritation was noted in all treated eyes at the 48 hour observation.
- All treated eyes appeared normal at the 72 hour observation.
Other effects:
All animals showed expected gain in bodyweight during the study.

Any other information on results incl. tables

Table 7.3.2/1: Eye irritation response data for each animal at each observation time

Score at time point

Cornea

Iris

(/2)

Conjunctivae

Opacity

(/4)

Area

(/4)

Redness

(/3)

Chemosis

(/4)

Discharge

(/3)

1 h

0 / 0 / 0

0 / 0 / 0

1 / 0 / 0

2 / 2 / 2

2 / 1 / 1

1 / 1 / 1

24 h

0 / 0 / 0

0 / 0 / 0

1 / 0 / 0

2 / 2 / 1

1 / 1 / 1

0 / 1 / 0

48 h

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

1 / 1 / 1

0 / 1 / 0

0 / 0 / 0

72 h

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

0 / 0 / 0

Mean 24, 48 and 72 h

0.0 / 0.0 / 0.0

0.0 / 0.0 / 0.0

0.3 / 0.0 / 0.0

1.0 / 1.0 / 0.7

0.3 / 0.7 / 0.7

0.0 / 0.3 / 0.0

Reversibility

 -

 -

Completely

reversible

Completely

reversible

Completely reversible

Completely reversible

Average time (unit) for reversion

-

-

48 h

72 h

72 h

48 h

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the experimental conditions of this study, the test item is not classified as eye irritant according to Regulation (EC) No. 1272/2008 (CLP) and to GHS.
Executive summary:

In an eye irritation study performed according to the OECD Guideline No. 405, and in compliance with GLP, 0.1 mL of undiluted test item was instilled into the right eye of 3 male New Zealand White(Hsdlf:NZW) strain rabbits. The upper and lower eyelids were held together for about one second immediately after application, to prevent loss of the test item, and then released. The left eye remained untreated and served as control. The eyes were examined and the changes were observed at 1, 24, 48, and 72 h after treatment and graded according to the Draize method.

 

No corneal effects were noted during the study. Iridial inflammation was noted in one treated eye one and 24 hours after treatment. Moderate conjunctival irritation was noted in all treated eyes one hour after treatment. Moderate conjunctival irritation was noted in one treated eye with minimal conjunctival irritation noted in two treated eyes at the 24 hour observation. Minimal conjunctival irritation was noted in all treated eyes at the 48 hour observation. All treated eyes appeared normal at the 72 hour observation.

 

Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 0.0 / 0.0 / 0.0 for cornea score; 0.3 / 0.0 / 0.0 for iris score; 1.0 / 1.0 / 0.7 for conjunctivae score and 0.3 / 0.7 / 0.7 for chemosis score.

 

Under the experimental conditions of this study, the test item is not classified as eye irritant according to Regulation (EC) No. 1272/2008 (CLP) and to GHS.

This study is considered as acceptable and satisfies the requirement for eye irritation endpoint.